Bhupinder Singh Kalra

Efficacy of Antidepressants as Analgesics: A Review

Persistent pain disorders are usually not adequately alleviated by nonsteroidal anti‐inflammatory drugs or other simple analgesics. Use of antidepressants as adjuvant therapy for the control of persistent pain is currently being practiced in disorders such as fibromyalgia, neuropathic pain, rheumatoid conditions, low back pain, and headache. This review describes the various mechanisms of analgesic activity of antidepressants along with their efficacy and tolerability profiles. Meta‐analyses and clinical studies of these agents were retrieved through the use of MEDLINE, Google scholar, and Cochrane databases. Antidepressants are effective in both neuropathic and non‐neuropathic pain and have diverse mechanisms independent of their antidepressant effects. Tricyclic antidepressants (amitryptiline, nortryptiline, desipramine) are effective compounds in the treatment of neuropathic pain, fibromyalgia, low back pain, and headaches. Studies are ongoing for the dual serotonin norepinephrine reuptake inhibitors (duloxetine, venlafaxine) in several persistent pain conditions and these may be recommended in neuropathic pain, migraines, and fibromyalgia. Evidence suggests that although the analgesic effects of selective serotonin reuptake inhibitors (fluoxetine, paroxetine, citalopram) are limited and inconsistent, yet they have a superior tolerability profile compared with tricyclic antidepressants.

Cytochrome P450 enzyme isoforms and their therapeutic implications: an update.

Clinicians should be cognizant of potential drug drug interactions and become familiar with the substrates, inhibitors and inducers of the common enzymatic pathways responsible for drug metabolism. Our knowledge of and ability to predict drug interactions have improved with growing understanding of substrates, inhibitors and inducers of cytochrome P450 (CYP-450) isoenzymes. These isoenzymes are a major determinant of the pharmacokinetic behavior of numerous drugs. In addition to inhibition and induction, microsomal drug metabolism is affected by genetic polymorphisms, age, nutrition, hepatic disease and endogenous chemicals. Prescribing physicians by understanding the unique characteristics of these isoenzymes may better anticipate and manage drug drug interactions.

Efficacy of metabolic modulators in ischemic heart disease: an overview.

Myocardial ischemia results in a decrease in oxygen supply to the heart, leading to cardiac dysfunction. Present therapeutic strategies for treating myocardial ischemia or infarction focus on maintaining coronary artery patency by either fibrinolysis or primary percutaneous intervention. Although these approaches have dramatically improved the prognosis in patients with angina pectoris and myocardial infarction, the complication of myocardial ischemia remains a major cause of mortality and morbidity worldwide. A novel approach that entails improving and optimizing cardiac energy metabolism of the ischemic myocardium by pharmacologically manipulating different metabolic pathways in the heart holds promise in limiting myocardial damage. Metabolic support of the ischemic myocardium is aimed at increasing glycolysis and residual oxidative phosphorylation of glucose along with decreasing fatty acid oxidation. This review discusses the various metabolic modulators, both conventional and new, along with documented evidence in both acute and chronic angina.

Belimumab: targeted therapy for lupus

Systemic lupus erythematosus (SLE), a complex autoimmune disease with multisystem involvement, is characterised by recurring flares and remissions throughout the course of illness. The agents currently being used for management include corticosteroids, antimalarials and various immunosuppressants. Belimumab, a B lymphocyte stimulator (BLyS) inhibitor has been recently approved for the treatment of SLE. This review aims to discuss the role of belimumab in the treatment of SLE and the trials leading to its FDA approval. Belimumab demonstrated high degree of activity in patients with autoantibody‐positive active SLE disease on a stable treatment regimen. There was a significantly greater response compared to placebo as assessed with the SLE Responder Index (SRI) in two randomized, double‐blind, phase III trials (BLISS‐52 and BLISS‐76). The treatment was well tolerated. Additional studies are required to evaluate belimumab in special populations and assess its long‐term safety. This therapy could change the focus of management from symptomatic treatment to targeting an important step in the disease pathogenesis. It could enable development of treatment which could halt long‐term progression, minimize target organ damage and thus provide a better quality of life for these patients.

Antidepressant-Like Activity of Tramadol in Mice

Objective: To evaluate antidepressant-like effect of tramadol in mice. Materials and Methods: Tramadol was administered at three different doses (10, 20, and 40 mg/kg, i.p.) once daily for 7 days to Swiss albino mice of either sex. The immobility period of control and drug-treated mice was recorded in forced swim test (FST). The antidepressant effect of tramadol was compared to that of fluoxetine (20 mg/kg, i.p.), administered for seven successive days. Results: Tramadol produced significant antidepressant effect at all the three (10, 20, and 40 mg/kg) doses, as indicated by reduction in immobility times of drug-treated mice compared to control mice. The efficacy of tramadol at doses of 10 and 20 mg/kg was comparable to that of fluoxetine, but antidepressant activity in animals administered with tramadol 40 mg/kg was significantly less as compared to fluoxetine-pretreated mice. Conclusion: The results of the present study indicate antidepressant-like activity of tramadol.

Evaluation of antidepressant activity of tramadol in mice

Objective: To evaluate antidepressant like effect of tramadol in mice. Materials and Methods: Tramadol was administered at three different doses (10,20 and 40 mg/kg, i.p) once daily for 7 days to Swiss albino mice of either sex. The immobility period of control and drug treated mice were recorded in tail suspension test (TST).The antidepressant effect of tramadol was compared to that of fluoxetine (20 mg/kg, i.p), administered for seven days. Results: Tramadol produced significant antidepressant effect at all the doses, as indicated by reduction in immobility times as compared to control. The efficacy of tramadol at doses of 20 and 40 mg/kg was comparable with that of fluoxetine. Tramadol at 10 mg/kg dose showed significantly less antidepressant activity compared to fluoxetine. Conclusion: The results of the present study indicate antidepressant like activity of tramadol.

Evaluation of gastric tolerability, antinociceptive and antiinflammatory activity of combination NSAIDs in rats

BACKGROUND Non-steroidal antiinflammatory drugs (NSAIDs) are one of the most commonly prescribed drugs in clinical practice. Presently, several varieties of fixed dose combinations (FDCs) of NSAIDs are available over the counter and are being prescribed too. There is paucity of literature regarding comparative efficacy of these combinations against their individual component. Various clinical studies have documented increased incidence of gastric ulcerations with usage of more than one NSAID simultaneously. OBJECTIVES To study gastric tolerability, antinociceptive and antiinflammatory activity of combination NSAIDs in rats. MATERIALS AND METHODS Gastric tolerability of different NSAIDs was observed after administration of drugs for 7 days orally. On 7 th day, 4 h after drug administration, rats were sacrificed and stomach mucosa was examined for ulcerations. Analgesic or antinociceptive activity of single and combination NSAIDs was evaluated using Writhing test model. For induction of writhing, 4% normal saline (hypertonic saline) was injected (0.1 ml/10 gm) intraperitoneally. Evaluation of antiinflammatory activity for FDCs of NSAIDs was done by using rat paw edema model with the aid of plethysmometer. Paw edema was induced by injecting 0.1 ml of 1% formalin in sub-planter region of hind paw. RESULTS Analgesic activity was found to be enhanced or significant only in the group pretreated with combination of nimesulide with ibuprofen as compared to ibuprofen-alone group (P = 0.01). Decrease in mean paw edema (antiinflammatory activity) was not significant in rats pretreated with combination NSAIDs as compared to NSAID-alone group. Mean gastric ulcer index was significant in groups pretreated with diclofenac alone (P = 0.03) and in combination groups of nimesulide with diclofenac and ibuprofen with paracetamol as compared to control (P = 0.03, P = 0.007). CONCLUSION Addition of ibuprofen to paracetamol and combining diclofenac to nimesulide, significantly increased severity of gastric ulcerations. Fixed dose combination does not possess additional analgesic activity over their individual components, only exception being combination of nimesulide with ibuprofen, which has additional analgesic activity over ibuprofen alone, and this combination was not found to be ulcerogenic. Antiinflammatory activity of ibuprofen, paracetamol and nimesulide was significantly enhanced after addition of diclofenac.

Efficacy of Sodium Valproate and Haloperidol in the Management of Acute Mania: A Randomized Open-Label Comparative Study

This study was carried out to compare the efficacy of intravenous sodium valproate with intramuscular haloperidol in patients with acute mania. A total of 30 patients meeting DSM‐IV criteria for acute manic episodes were enrolled. They were randomly assigned to 2 groups of 15 patients each. Both groups were treated twice daily with haloperidol (10 mg, intramuscular) and sodium valproate (500 mg, intravenous). The patients were assessed on days 1, 5, 9, and 13. Improvement in symptoms was assessed by reduction in the Young Mania Rating Scale (YMRS). Outcome criterions for analysis were latency of response and remission; additional drugs were required for sedation. At the end of the 2‐week study period, overall response rate in both the groups was similar (P > .1). In comparison to haloperidol group, patients treated with sodium valproate showed faster response, and on day 5, significant reduction in YMRS score was observed in the group treated with sodium valproate (P < .05). Total amount of lorazepam was less in patients treated with sodium valproate. Extrapyramidal symptom episodes were observed in 60% of patients treated with haloperidol. Sodium valproate in the treatment of acute mania is as efficacious as haloperidol but provides a faster response. It is safer compared to haloperidol.

Evaluation of the analgesic and anti-inflammatory activity of fixed dose combination: non-steroidal anti-inflammatory drugs in experimental animals.

BACKGROUND In India, a number of fixed dose drug combinations of non-steroidal anti-inflammatory drugs (NSAIDs) are available, often as over-the-counter products. These combinations are being prescribed too. Evidence for efficacy of NSIAD fixed dose combination is lacking. OBJECTIVES The current study was undertaken to assess the analgesic and anti-inflammatory efficacy of these combinations over their individual components. MATERIALS AND METHODS The study used three NSAIDs viz; paracetamol, ibuprofen and diclofenac sodium, alone or in combination with paracetamol. Animals were divided into six groups with six animals in each group. Analgesic activity was tested by writhing test and paw edema model was used to assess the anti-inflammatory activity. The test drugs were administered orally 30 min prior to injecting 0.6% solution of glacial acetic acid intraperitoneally for writhing test. For paw edema test, after 30 min of drugs administration, animals were injected with 0.1 ml of 1% carrageenan in subplanter region for inducing inflammation. Paw volume was again measured at baseline and after 3 h of subplanter injection of 1% carrageenan. RESULTS The analgesic and the anti-inflammatory activity of paracetamol and ibuprofen combination were significantly greater than the individual agents when used alone. However, no significant difference in the analgesic or anti-inflammatory activity was found between diclofenac sodium and its combination with paracetamol. It was observed that diclofenac sodium was the most efficacious of the analgesics tested. Combining paracetamol with diclofenac did not show superior analgesic activity compared to diclofenac alone (P = 0.18). CONCLUSION Combining paracetamol with ibuprofen enhances analgesic/anti-inflammatory activity over their individual component but potentiation of analgesic activity of diclofenac was not seen when paracetamol was added to it.

Prescription pattern in patients with rheumatoid arthritis in a teaching tertiary care hospital

Objective: This study was conducted, with the aim to analyze the pattern of use of antirheumatic drugs in a Tertiary Care Hospital in Delhi, India. Methodology: The study was carried out in 150 patients who were on treatment with antirheumatic drugs at least for the past 6 months. Patient demographic details, duration of illness, comorbid conditions, drugs prescribed, adverse drug reactions (ADRs), and usage of complementary and alternative medicine (CAM) were used to analyze the pattern of drug use. Results: In our study, we observed that in patients with rheumatoid arthritis (RA), the most commonly prescribed disease-modifying antirheumatic drugs (DMARD) was methotrexate followed by hydroxychloroquine and sulfasalazine. DMARD combination with 3 drugs (59.3%) was the most common regimen followed by DMARD combination with 2 drugs (32.6%). Polypharmacy was seen in most of the prescriptions, but 76.3% of the drugs were from Essential Medicine List of Government of National Capital Territory, Delhi. About 40.7% of the prescriptions were prescribed by generic names. CAM was used by 13.3% of the study patients. Conclusion: The drug use pattern in RA was found to be DMARDs dependent. The concomitant use of three DMARDs was the preferred therapy. Biologics were not being used although indicated as per guidelines. ADRs associated with RA treatment were generally mild in severity and involved gastrointestinal tract.